The literature is replete with proposals from researchers attempting to extend the active life of compounds possessing physiological activities by coupling the compounds to large natural and synthetic materials. None of these attempts, however, have met with singular success.
U.S. Pat. No. 3,704,282 to Sidney Spector, for instance, describes the failure of others in preparing an antigen by diazotizing aminoadrenaline and coupling the resulting diazoadrenaline with a serum albumin. The resulting product was reported as being inactive because of the absence of the essential catechol function of aminoadrenaline and as not being an antigen specific for adrenaline, containing most likely an oxidized catechol function such as an orthoquinone. Spector emphasizes that this product is of limited utility as an effective antigen and chooses instead to bond the biologically active compound, i.e., the catecholamine to the polymer through a peptide linkage.
Water-soluble polymer-hormone products containing a hormone covalently bonded to a copolymer of an olefinically unsaturated polycarboxylic acid and an olefin also are reported in Schuck et al., U.S. Pat. No. 3,679,653. In the teachings of Schuck et al., the hormone is covalently bonded to the polymer through either amino, hydroxyl, or sulfhydryl groups of the hormone. Specifically, the preferred polymers are either ethylene/maleic anhydride copolymers or styrene/maleic anhydride copolymers with the preferred hormone being either peptidic or proteinaceous.
Another method for covalently bonding a hormone to the polymer has been set forth by Lennart Kagedal in U.S. Pat. No. 3,788,948. In accordance with the teachings of Kagedal, the biologically active hormone is covalently bonded to a polysaccharide by a urethane group. E. Katchalski, in his article "Preparation, Properties and Applications of Some Water-Insoluble Derivatives of Proteolytic Enzymes" in Polyaminoacids, Polypeptides and Proteins, 1962, pp. 283-289, describes proteolytic enzymes bonded via azo linkages to copolypeptides. The products of Katchalski, however, are water-insoluble immobilized enzymes designed as biological catalysts which obviates their use as physiologically active compounds. pg,3
Thus, each of the aforementioned methods fails to provide a product which possesses the desired physiological activity while simultaneously providing long-lasting effects.